JP5690740B2 - treatment - Google Patents

Description

  The present invention relates to methods and devices for medical and / or cosmetic procedures. In particular, one aspect of the present invention is directed to a method for reducing peripheral vascular resistance in a patient's blood circulation. Another aspect of the invention relates to a method for treating a disease characterized by increased peripheral vascular resistance. The invention also relates to a device for carrying out the method. A further aspect of the invention relates to other uses of the device.

  Patent Document 1 describes a method and device for reducing or treating deep vein thrombosis (DVT). The device includes an electrode that is secured to the patient's leg and used to provide electrical stimulation to the muscle. Preferably, the electrodes are arranged to stimulate the outer and / or inner popliteal nerves that contract the calf muscle. As a result, a muscle vein pump can be moved to promote blood circulation by muscle contraction within the muscle vein pump, thereby reducing the risk of thrombus in the limb. Other muscle vein pumps include foot pumps, and the device can also be used to stimulate foot pumps in addition to or in place of calf pumps. Preferably, the device is used to induce isometric contraction of the muscle so that the muscle vein pump is moved, but calf movement from that stimulation is reduced or avoided.

  As described in U.S. Patent No. 6,057,059, the use of the device in the manner described therein has been demonstrated to increase venous drainage in the leg and increase cortical blood flow in the long bones of the leg. ing. Due to these effects, the device has symptoms other than DVT characterized by impaired venous blood flow (including ulcers, varicose veins, ischemia, edema, phlebitis, osteoporosis, peripheral vascular disease, coronary artery disease, hypertension). Use for treatment has also been proposed. These diseases are considered treatable based on their ability to increase venous blood flow.

International Publication No. 2006054118

J. et al. Truta, “The role of the vessels in osteogenesis”, J. Am. Bone Joint Surg. Br. 1993

  Surprisingly, it has been found that the device and similar devices can be used to change a patient's blood flow pattern.

  Using electrical stimulation of muscles provides evidence that not only can the calf muscle vein pump be moved to increase venous drainage, but also change the patient's blood flow pattern. In particular, arterial diastolic reflux can be reduced or prevented. This is thought to be the result of a reduction in peripheral vascular resistance. Although enhancement of blood flow has been known for some time, the discovery that blood flow can be significantly altered is unexpected and provides multiple new uses for the device.

Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Figure 3 shows arterial blood flow measurements of three separate test subjects at different stimulation levels. Compare the speed of skin blood flow between stimulated and unstimulated limbs at different stimulation levels. Compare the skin temperature of unstimulated and unstimulated limbs at different stimulation levels. Figure 6 shows oxyhemoglobin levels measured by infrared spectroscopy of the tibia during a stimulation cycle. Shows changes in deoxyhemoglobin levels in all patients during stimulation. A first desirable electrode configuration is shown. A second preferred electrode configuration is shown. A plurality of electrode configurations tested are shown. Figure 6 shows the asymmetric and symmetric waveforms that were tried. Results of electrode and waveform comfort tests are shown. Results of electrode and waveform comfort tests are shown. 1 shows a drawing of an embodiment of a device according to the invention. 1 shows a drawing of an embodiment of a device according to the invention. 1 shows a drawing of an embodiment of a device according to the invention. 1 shows a drawing of an embodiment of a device according to the invention.

  According to a first aspect of the invention, a method is provided for reducing peripheral vascular resistance in a patient's leg. The method includes applying to the plurality of leg muscles one or more electrical stimuli sufficient to cause an isometric contraction of the leg muscles. Also provided is a method of reducing or preventing diastolic reflux of a patient's leg artery. The method includes applying to the plurality of leg muscles one or more electrical stimuli sufficient to cause an isometric contraction of the leg muscles.

  The reduction of peripheral vascular resistance and the reduction of diastolic reflux allows the treatment of additional symptoms that were not previously known to be treatable by electrical stimulation of muscles. In particular, the present invention also provides a method for treating diseases characterized by increased peripheral vascular resistance. Such diseases include lower limb arterial disease (peripheral arterial disease), lower limb lymphatic drainage disorder, heart disease, restless leg syndrome (Witmark Ekbon syndrome), lower limb soft tissue damage (skin and muscle bruises, micro-lacerations, (Including sports injuries) and inflammation. The present invention provides methods for treating each of these diseases. In addition, the reduction of peripheral vascular resistance is considered to be effective in sports training and rehabilitation regardless of whether or not the subject is injured.

  For example, the method of the present invention can be used to reduce recovery time after a sports event. After such an event (eg, a football game or competition race), it may take several days for performance to return to the pre-event level, even if the participant is not injured. The method of the present invention is believed to be effective in reducing this recovery time and is applied, for example, 2-24 hours after an event or between training sessions.

  The method is also effective in other conditions where blood retention can be a problem. In particular, it is for preventing or avoiding G-LOC (gravity-induced loss of consciousness). In such embodiments, the method includes the steps of monitoring the gravity experienced by the subject and adjusting the stimulus in response to the monitored change in gravity (eg, increasing gravity is the frequency of the stimulus). Can be increased). Other applications include maintaining blood flow under low gravity during space travel, reducing the possibility of blood retention while standing for a long time (eg parade soldiers), Reduction or prevention.

  The leg muscles are preferably calf muscles, but in certain embodiments of the invention, stimulation of the ankle and / or foot musculature may be used instead or additionally. Leg muscles are preferably included in a muscle vein pump (eg, calf pump, foot pump and / or thigh pump).

  Stimulation can be applied directly to the muscle or indirectly through appropriate neural stimulation. For example, a preferred method is by accessing a nerve group within the popliteal area (the nerve group in this area is generally easily accessible to each person with minimal energy requirements, regardless of weight). Indirect stimulation of lower limb muscle tissue. Unless stated otherwise, it is to be understood that all references to muscle stimulation herein include both direct and indirect stimulation.

  A possible effect of a single contraction of the calf muscle is plantar flexion. In a sitting individual, this can raise the knee and make this process stand out. Isometric contractions ensure that opposing muscles or groups of muscles are stimulated such that the resulting limb movement is reduced or eliminated. Stimulation can be applied directly to the posterior calf muscle, conveniently the soleus and / or gastrocnemius. Indirect stimulation of the lower limb muscles can be achieved by electrical stimulation of the lateral popliteal nerve in the area of the popliteal area (especially the medial edge of the biceps femoris, the back of the ribs inside the biceps tendon) ). Furthermore, indirect stimulation of the lower limb muscles can be achieved by electrical stimulation of the medial popliteal nerve (located inwardly from the lateral popliteal nerve in the region of the popliteal region).

  The second stimulus can be applied to the shin muscle, conveniently the anterior tibial muscle. Preferably, the second stimulus is applied simultaneously with the stimulus applied to the calf muscle. Although the tibial muscle stimulation alone promotes blood flow to some extent, the main purpose of this second stimulation is to prevent unwanted limb movement. The application of stimulation only to the posterior calf muscle may have the undesirable side effect of causing ankle joint movement. Application of stimuli to the shin muscles counteracts ankle joint movement caused by calf muscle contraction, keeping the ankle and knee joints relatively stationary.

  Instead, stimulation of the outer popliteal nerve in the area of the popliteal region has the advantage that the contraction of the posterior and anterior lower limb muscle groups starts from a single stimulation point. Such simultaneous stimulation results in isometric contractions so that the ankle and knee joints are typically not moved. In addition, stimulation of the lateral popliteum also causes contraction of the leg muscles, thus causing a so-called “foot pump”. Furthermore, the surprising advantage of selective stimulation of the lateral popliteal nerve is that the resulting muscle contraction is completely compatible with standing and walking. A further advantage of this mode of indirect stimulation is the involvement of plantar muscles, which has been shown to contribute substantially to the clearance of blood from the lower limbs. In addition, nerve stimulation in this way (not directly against muscle) makes the method feel little or no skin sensation or discomfort when used to stimulate muscle contraction. Can be operated.

  In clinical environments where standing and walking are not assumed, the medial popliteal nerve may be stimulated separately or in combination with stimulation of the lateral popliteal nerve. The preferred version of the dual stimulation of the medial and lateral popliteal nerves results in almost maximum contraction of all lower limb muscle tissue, leading to increased efficiency and activity of both calf and foot venous pumps, and thus towards the abdomen Brings movement of venous blood out of the lower limbs to the center.

  Preferably, the method comprises repeatedly applying electrical stimulation to the muscle.

  A typical electrical stimulus may be a current between 0 and 100 mA, preferably between 0 and 50 mA, more preferably between 1 and 40 mA, most preferably between 1 and 20 mA. Another example of stimulation current is between 15 and 30 mA.

  The stimulus can be an AC waveform, but is preferably a DC waveform, more preferably a pulsed DC waveform. The stimulus may have a frequency of 0.01 to 100 Hz, preferably 0.1 to 80 Hz, more preferably 0.1 to 50 Hz, and even more preferably 0.1 to 5 Hz. The most preferable frequency is 0.5 to 5 Hz, 1 to 5 Hz, preferably 1 to 3 Hz, for example, 1, 2 or 3 Hz. In other embodiments, the frequency can be 30 to 60 Hz, more preferably 40 to 50 Hz. Alternatively, stimuli with a frequency of 0.1 to 1 Hz, or 0.33 to 1 Hz may be used. The exact desired frequency may depend on, among other things, the purpose of the method, the desired physiological behavior desired to occur, general physical conditions, age, sex, and patient weight.

  A specific example of a preferred stimulus is 20 mA at a frequency of 5 Hz, 30 mA at 3 Hz, and 28 mA at 1 Hz. Of course, other stimuli can also be used.

  Stimulation may be applied over a period of between 0 and 1000 ms, between 100 and 900 ms, between 250 and 750 ms, between 350 and 650 ms, or between 450 and 550 ms. In certain embodiments, the stimulus can be applied for up to 5000 ms, up to 4000 ms, up to 3000 ms, up to 2000 ms. Other time periods may be used, but again, depending on the details of the patient or intended behavior. Another preferred period is 70 to 600 ms. In certain embodiments, shorter time periods may be used, for example 25 μs to 800 μs.

  The characteristics of the stimulus can change over time. For example, the current of a single stimulus can increase with the duration of the stimulus. Preferably, the increase is gradual towards the peak, after which the stimulus can be maintained at the peak, truncated at the peak, or gradually decreased. Instead, when repetitive stimuli are applied, the characteristics of the stimuli can vary between different stimuli. For example, sequential stimuli can be applied at increasing current levels. Again, the sequential stimulus is gradually headed to the peak and subsequently maintained at that peak or may decrease from the peak. The increasing cycle of stimulation can be repeated multiple times. In a preferred embodiment, each stimulus is a single pulse rather than multiple short pulses.

  Stimulation can be applied to multiple locations on the muscle. For example, the stimulus can be applied along the main axis (long axis) of the leg. Such stimuli can be applied simultaneously or preferably sequentially so that a 'wave' of stimuli travels along the leg. Preferably, such waves travel above the patient's body. This wave effect serves to generate a corresponding wave of muscle contraction that helps to promote blood flow away from the leg. However, in a preferred embodiment of the present invention, stimulation is applied to a single point on the leg to stimulate the lateral popliteal nerve as described above. A “single point” can also include stimulation with more than one electrode, for example, a pair of positive and negative electrodes can be felt by a user as a point rather than over a region of high stimulation. It is a case where it is used with sufficiently small intervals (for example, 1 to 3 cm, or 2 cm at the maximum).

  Also provided is a method for diagnosing symptoms characterized by increased peripheral vascular resistance. The method includes applying one or more electrical stimuli to a plurality of leg muscles at a first frequency and / or current sufficient to cause isometric contraction of the leg muscles; Monitoring blood flow to determine if diastolic reflux of arterial flow is reduced or prevented and / or if peripheral vascular resistance is reduced.

  The method comprises the steps of repeating and monitoring stimulation at a second frequency and / or current and the frequency and frequency required to achieve reduction or prevention of diastolic regurgitation of arterial flow and / or reduction of peripheral vascular resistance. And / or determining the level of current. The level at which this occurs can give information about the severity of the symptoms.

  The method comprises comparing the level of frequency and / or current required to achieve reduction or prevention of diastolic regurgitation of arterial flow and / or reduction of peripheral vascular resistance with that required for healthy control patients. Further provisions may be made. Again, this can help diagnose the symptoms or give some indication of the severity of the symptoms. Healthy control patients can be selected to be otherwise comparable to patients.

  The present invention also provides a method for promoting circulation in patients with cardiac abnormalities. The method includes applying to the plurality of leg muscles one or more electrical stimuli sufficient to cause an isometric contraction of the leg muscles. As mentioned above, electrical stimulation of the myovenous pump facilitates changes in blood flow patterns, which can be useful for patients with cardiac abnormalities. Heart abnormalities include cardiac arrest, suspected cardiac arrest, arrhythmia, bradycardia, and angina. The method can also be used as an aid to defibrillation in the case of cardiac arrest. Also provided is a device for promoting circulation of a patient having a cardiac abnormality. The device provides at least one electrode for applying electrical stimulation to a patient's opposing leg muscle, a power source connectable to the electrode, and sufficient electrical stimulation to cause the leg muscle to contract isometrically. And a control means for operating the electrode to be applied to the leg muscle. The present invention also provides a kit comprising a combination of such a device and a defibrillator. Alternatively, the device can include a defibrillator.

  A further aspect of the invention relates to alteration of cortical blood flow in the bone. As described in Patent Document 1, an isometric method of muscle stimulation has been shown to promote cortical blood flow. Later, it was discovered that bone oxygenation and bone perfusion were increased by use of the present method and demonstrated herein. This enables more effective transport of the drug to the bone, and particularly includes drugs for the treatment of bone diseases such as osteoporosis. Thus, according to a further aspect of the invention, a method is provided for improving the administration of a medicament for the treatment of bone diseases. The method includes administering a drug to a patient and applying to the plurality of leg muscles one or more electrical stimuli sufficient to cause isometric contraction of the leg muscles to enhance bone perfusion. Stages. The bone disease can be osteoporosis. Kits for the treatment of bone diseases are also provided. The kit includes an agent for treating bone disease, at least one electrode for applying electrical stimulation to the opposing leg muscles of the patient, a power source connectable to the electrodes, and the leg muscles isometrically. And a control means for actuating the electrodes to apply sufficient electrical stimulation to the leg muscles to contract.

  Improved perfusion can also help improve the transport of contrast agents (eg for medical imaging purposes) to tissues such as bones, tendons, ligaments. Accordingly, one aspect of the present invention provides a method for improving contrast agent transport. The method comprises administering a contrast agent to a patient and one or more electrical stimuli sufficient to cause multiple leg muscles to cause isometric contraction of the leg muscles to enhance perfusion of the contrast agent. Providing a step.

  A further aspect of the invention relates to cosmetic therapy. As demonstrated herein, the use of the method increases peripheral blood circulation, particularly in the skin. The method also increases the temperature of the skin where circulation is enhanced. These effects can be effective in personal cosmetic procedures. For example, the effect includes reduction of cellulite or collagen deposition, improvement of skin tone, and improvement of skin condition. Accordingly, the present invention provides a method for cosmetic treatment of a patient. The method includes applying sufficient electrical stimulation to at least one leg muscle of the patient to cause the leg muscle to contract isometrically. The cosmetic treatment may be selected from reducing cellulite or collagen deposition, improving skin tone, or improving skin condition. A kit for beauty therapy is also provided. The kit provides at least one electrode for applying electrical stimulation to the opposing leg muscles of the patient, a power source connectable to the electrodes, and sufficient electrical stimulation to cause the leg muscles to contract isometrically. And a device with control means for actuating the electrodes for application to the muscle.

  The device described in Patent Document 1 includes specific electrode configurations that can be used. In this application, data demonstrating a specific novel electrode configuration that feels more comfortable for the user is demonstrated. Accordingly, the present invention provides a positive and negative electrode for applying electrical stimulation to the opposing leg muscles of a patient, a power source connectable to the electrodes, and sufficient electrical power to cause the leg muscles to contract isometrically. There is provided a device comprising control means for actuating an electrode to apply a stimulus to a leg muscle. Here, one electrode substantially surrounds the other electrode.

  “Substantially enclose” means that one electrode comprises at least 66%, preferably at least 75%, more preferably at least 85%, more preferably at least 90%, most preferably 100% around the other electrode. It means enclosing. Although it is preferred that one electrode is completely surrounded by the other electrode, it is not essential.

  This electrode configuration has been found to lead to improved comfort perception of the user.

  Preferably, the positive electrode substantially surrounds the negative electrode.

  In some embodiments, the electrodes are concentric or substantially concentric. In other embodiments, the electrodes are substantially elongated and may preferably be substantially quadrilateral (such as a rectangle), C-shaped, or U-shaped.

  Preferably, one electrode has a larger area than the other electrode, and preferably the larger electrode is a positive electrode.

  Preferably, the control means is configured to apply an AC electrical stimulus. Preferably, the waveform of the current is asymmetric, conveniently the waveform provides a short-term initial (positive) pulse with high intensity, followed by a long-term (negative) pulse with low intensity. The areas in the curves of the two pulses are equal. In one embodiment, the initial pulse is of a substantially square waveform.

  A further aspect of the present invention is the ability to connect to the positive and negative electrodes for applying electrical stimulation to the nerves distributed in the opposing leg muscles of the patient to cause isometric contraction of the leg muscles. Provided is a device with a simple power supply and control means for actuating the electrodes.

  Preferably, the positive and negative electrodes are spaced 20-30 mm apart, but this has been found to provide a favorable stimulation level.

  The electrodes can be of different sizes, preferably the positive electrode is larger than the negative electrode. This provides a higher charge density at the motion point and a higher overall capacitance. The electrode can be a silver electrode. The electrodes can be continuous or can include holes, for example, the electrodes can be solid electrodes or meshed.

  In a preferred embodiment, the device comprises a flexible substrate to which electrodes are attached, a power source, and control means. The control means is, for example, a PCB configured to actuate the electrodes appropriately. The power source can be a battery. The substrate is preferably flexible but non-stretchable, thereby reducing the risk of electrode cracking or breakage. For example, the substrate can be a thermoplastic elastomer.

  The electrodes can be printed directly on the substrate by conventional printing methods (eg, pad or tampo printing). Similarly, conductive tracks can be printed on the substrate if desired.

  The substrate can be an elongated strip or tongue, with the electrodes spaced apart along the strip. In such a configuration, the conductive track may need to be placed near the nearer electrode and farther away from the power source. In such a configuration, the device may comprise one or more insulating strips or regions arranged to separate the conductive track from the nearer electrode, the insulating strip or alternatively the insulating strip instead. May be disposed along the edges of the substrate strip to prevent leakage of current out of the region of the substrate strip. Alternatively or additionally, the substrate can be provided with a recessed groove in which a conductive track can be placed, which serves to separate the track from the substrate.

  In certain embodiments, the device may be configured to be implantable in a patient (eg, implantable subcutaneously). This is effective in chronic conditions where long-term use of the device is required.

  The device further comprises a conductive gel covering the electrodes. Preferably, for ease of manufacture and structural integrity, the gel can be a single piece covering both electrodes. Based on the bulk resistivity and geometry of the material, it has been demonstrated that a single piece of gel can be used such that the leakage resistance is much greater than the transport resistance. Examples of gels that can be used include hydrogels and silicones.

  The device can be assembled as follows. The flexible substrate may be formed with a generally flat and elongated strip and a recess forming a compartment. Then, the electrodes and conductive tracks are printed on the substrate, and the power supply and control means are placed in the recess. As a result, all the electrical connections are connected. The recess is then closed, for example, by ultrasonically welding the cover so that the power source and control means are sealed within the recess. Finally, the gel is placed on the electrode.

  The device may further comprise a position mark that assists in correct placement during use.

  The device may include a push button to activate or deactivate the device. The control means may be configured to provide a plurality of operating modes (eg, different stimulation characteristics). These modes can be switched using a push button. The device may include display means such as light or LED to indicate the selected mode of operation.

  Preferably, the device is for reducing diastolic backflow.

  In certain embodiments, the device may be disposable, for example after a single use.

  The device is sufficiently small and lightweight. For example, the device has a length of 10 cm or less, a weight of 100 g or less, preferably 20 g or less, and has high portability.

  In use, the device may operate with little or no skin sensation or discomfort when actuated to stimulate muscle contraction.

[Detailed description of the drawings]
A device for electrically stimulating leg muscles is described in detail in U.S. Pat. No. 6,057,049, and reference is made to that document for a complete description of the device. The present invention is primarily based on a number of unexpected effects observed from the use of the device and similar devices, and a particularly preferred embodiment of the device will be described.

  Briefly described, one embodiment of a device such as that disclosed in US Pat. No. 6,053,836 includes a loop of stretchable material that can be worn on the user's leg in use. First and second electrodes connected by conductive wires to a cradle integrated with the elastic material are disposed on the inner surface of the elastic material.

  A control module is mounted in the cradle and includes a power battery, a control processor and an external LED.

The control module is removable from the cradle and connects the cradle and control module by a pair of detents and corresponding recesses. The control module and cradle have a corresponding electrical contact surface and provide electrical communication between the control module and the first and second electrodes via a conductive wire.

  The control processor includes a timer module, a data storage unit, a program storage unit, and a logic unit.

  In use, the device operates as follows. The elastic loop is worn on the user's lower limb such that the first electrode contacts the calf muscle behind the lower limb and the second electrode contacts the muscle in front of the lower limb. When the control module is linked with the cradle, the device is automatically activated.

  The program storage unit is preinstalled with an operation program configured to operate the electrode every minute using a pulsed DC of 40 Hz at 20 mA for 0.1 second. Both electrodes are activated simultaneously. The timer module generates an appropriate time interval signal and the logic unit executes the program in the program storage unit.

  When the electrode is activated, the user's muscles are stimulated and contracted. The contraction of the posterior calf muscle is triggered by the first electrode to reduce blood retention by pumping blood from the leg using a calf pump. Anterior muscle contraction is caused by the second electrode to reduce unwanted movement of the ankle by offsetting the contraction of the posterior calf muscle. Simultaneously with each activation of the electrodes, the LEDs on the outer surface of the control module are also activated, giving a visual confirmation that the device is operating.

  The preceding description is that of the device of one embodiment. However, a suitable device for stimulating muscle can be constructed from conventional skin electrodes and a suitable power source. This type of test equipment is used in the following experiments.

[Experimental design]
Research Title: A study seeking the effect of a novel method to enhance lower limb blood flow in healthy adult volunteers. It is. The second problem is to evaluate changes in blood flow rate and blood volume accompanying changes in the intensity and level of electrical stimulation in duplex ultrasound and plethysmography.
Study design: Study of central physiological responses in healthy volunteers Stimulation application: The effects of electrical stimulation on blood flow in the lower limbs of healthy volunteers during a 4-hour long-term seating were investigated. Each subject finished their study seating in an industry standard aircraft seat. The stimulator used a custom stimulation protocol. Superficial electrical stimulation was applied to the lateral popliteal nerve located in the popliteal area.
Sample size: 30 volunteers

[Environmental condition]
The test was performed in a quiet, stable and windless environment with temperature and humidity controlled (24 ± 1 ° C., relative humidity 30-40%). Volunteers were instructed to have a light breakfast, avoid greasy meals, tobacco and caffeine, and refrain from intense exercise the night before. The volunteers were lightly dressed (underwear) and sat in a comfortable position with their knees bent.

  The effect of electrical stimulation on the blood flow in the lower limbs of healthy volunteers during a 4-hour long seat was examined. Each subject completed their study seating with an industry standard aircraft seat specially obtained for this study.

  The leg gap distance was set to 34 inches by alignment of the toe bars. It was strongly recommended that each subject be placed on the seat by a safety belt to keep the posture almost uniform and be passive as long as each person can tolerate.

[Physiological evaluation]
During this phase, the amplitude and frequency of the electrical stimulation was changed and the associated blood flow changes were recorded.

  Changes in lower limb blood flow were assessed using routine non-invasive plethysmography (optical plethysmography, strain gauge plethysmography, air plethysmography), transcutaneous oxygen, and, if possible, color flow duplex ultrasound .

  Changes in blood flow and blood volume as a function of protocol were compared to changes in blood flow and flow rate determined by volunteer muscle movement. In other words, volunteers were asked to do 10 plantar flexions (10 toe-lifting exercises with the heel on the ground). This is the maximum physiological response that can be obtained in the sitting position.

  Volunteers were asked to evaluate the acceptability and tolerability of electrical stimulation sequences using a questionnaire (oral evaluation score) and a scoring table (visual analog score). Discomfort was related to the normal measurement of blood pressure and was measured on the upper arm using a standard sphygmomanometer cuff.

  Following the 4 hour seating period, the volunteers were re-examined with duplex ultrasound to recheck deep vein status and exclude significant thrombus development. The study was conducted at two separate times for each subject and averaged them to reduce experimental bias.

[Stimulator]
The device generates various preset programs that correspond to different stimulation currents and pulse frequencies. The waveform is specifically designed for motor nerve stimulation, as opposed to direct muscle stimulation. The pulse amplitude is in the range of 1 mA to 40 mA at a frequency in the range of 1 Hz to 5 Hz, and deviates significantly from physical therapy and TENS protocols (generally applying substantially higher currents and frequencies).

  As shown in Table 1, a series of 15 different stimulation programs were applied to each subject in the course of each study according to a two-dimensional matrix of amplitude and frequency. The duration of each stimulation program was 5 minutes, followed by a 10 minute recovery phase, and the blood vessels were re-equilibrated before the next sequence.

  In each of the 15 programs, non-invasive blood flow and blood volume parameters were determined as described above with reference to levels observed during spontaneous muscle contraction and levels observed in the contralateral limb. It was measured.

[Example 1: Blood flow pattern]
Volunteer venous blood flow patterns were monitored using stimulated paw vascular ultrasound. Representative examples are shown in FIGS. FIG. 1a shows the stimulation of the first subject at 20 mA, 5 Hz, FIG. 1 b shows that at 5 mA, 5 Hz, and FIG. 1 c shows that without stimulation. FIG. 2a shows that of a second subject stimulated at 20 mA, 3 Hz, FIG. 2b is of the same subject immediately after stimulation, and FIG. 2c is of the subject at rest. FIG. 3a is for a third subject receiving 10 mA, 3 Hz stimulation, FIG. 3 b is at 1 mA, 3 Hz, FIG. 3 c is at 20 mA, 5 Hz, and FIG. 3 d is at 5 mA, 1 Hz. 3e is at 5 mA, 3 Hz, and FIG. 3f is the subject at rest.

  In these examples, there was a quadruple increase in venous blood flow rate from baseline. There was also a significant increase in the frequency of cephalic (toward the head) venous blood flow due to the application of the stimulus.

  The flow velocity of the superficial femoral artery is doubled, and the backflow component of the arterial flow waveform of the pulse wave is completely removed by applying the stimulus.

  Superficial femoral artery regurgitation is due to high resistance of peripheral blood vessels, and advance flow throughout the cardiac cycle suggests a significant reduction in peripheral vascular resistance.

  A decrease in total peripheral resistance (resulting from increased vascular pumping by the device) is indicated by laser Doppler and venous vascular ultrasound, which increases blood flow. The result is an increasing trend in heart rate output. It was also shown that there was no significant increase in heart rate (beats per minute). This is demonstrated by increased arterial blood flow and waveform changes.

  Importantly, because the increase in blood flow in the various tissues of the leg is proportional, there is an increase in blood flow in all tissues, and thus no 'borrowing' of blood from adjacent tissues. All tissues, skin, muscles, bones, etc. have increased blood perfusion.

  Blood flow resistance includes: arterial pressure, heart rate output, distribution of heart rate output to whole body organs, distribution of organ blood flow to various organ tissues, division of tissue blood flow between capillaries and arteriovenous anastomoses, capillaries Hydrostatic pressure can affect the distribution of blood flow within the cardiovascular system. All of this is up-regulated by a specific well-defined device.

  Analogous to this is exercise, which still reduces total peripheral resistance as the exercise load measured by oxygen consumption increases. The decrease in vascular resistance is accompanied by a gradual increase in heart rate output. The device mimics this phenomenon with minimal oxygen consumption compared to exercise without a substantial increase in workload.

  Furthermore, an increase in microcirculatory blood flow can also be explained by an increase in the use of previously closed or 'rested' capillary networks (available for local exchange). The effect of this is a further increase in tissue perfusion and peripheral vascular resistance.

  This is a new and unique observation and has a great impact on the cardiovascular system and vascular therapy.

  Thus, application of electrical stimulation can increase venous blood flow and reduce or prevent diastolic reflux in the artery. Note that this does not occur in all settings. FIG. 3d does not show the backflow when stimulated at 5 mA, 1 Hz.

  This effect has potential for a wide range of therapeutic and diagnostic applications. For example, since the effect occurs only in a particular setting, it is believed that the current and frequency at which the effect occurs in an individual patient can be characteristic of normal arterial flow and / or peripheral vascular resistance. This can be used to diagnose the presence and / or severity of a patient's circulatory disturbance. Therapeutically, correction of arterial flow and reduction of peripheral vascular resistance can be effective in treating a wide range of conditions such as ischemia, cardiovascular disease, ulcers and the like.

[Example 2]
The velocity of skin blood flow was measured using laser Doppler flow measurement (LDF, Laser Doppler Fluxmetry). The result is shown in FIG. LDF flux (blood velocity) is increased up to approximately 1000% in stimulated legs compared to baseline and unstimulated legs (indicating values near baseline levels).

[Example 3]
Skin temperature was measured in stimulated and unstimulated legs. The result is shown in FIG. There is a slight temperature increase for all stimuli in the stimulated leg compared to the unstimulated leg. The body temperature is caused by metabolism and blood flow. Since metabolism is not altered during stimulation, a slight increase in skin temperature is an indication of increased blood flow in the skin surface.

[Example 4]
Treatment of osteoporosis Approximately 2 million osteoporotic fractures occur every year worldwide (according to the World Health Organization, there were 1.66 million in 1990 and 6 million in 2050 each year). Expected to be). High-risk groups include older people and people with spinal cord injury.

  In healthy individuals, bone is regularly remodeled according to physical requirements. Osteoclasts remove minerals from the bone and resorb the collagen matrix, while osteoblasts promote the deposition of new collagen matrix and minerals.

  Over the last century, various theoretical models have been proposed for the mechanism by which the body controls bone density. In 1892, Wolf proposed that bone deposition followed a bone stress pattern. In Frost's 1987 "Mechanostat" theory, it was proposed that the bone be made to maintain a uniform strain under habitual loads.

  Models that explain why some people have problems maintaining bone density initially focused on nonuse. In older people, reduced bone use leads to lower stress and strain necessary to signal bone maintenance. More recently, however, it has been proposed that a vascular component exists for causation. Osteoporosis is caused by either reduced angiogenesis (which itself is exacerbated by nonuse), restriction of flow in existing blood vessels due to atherosclerosis, or simply a lower level of activity that results in less blood circulation. Occurs in people with impaired perfusion (Non-Patent Document 1).

  The present invention has the potential to alleviate vascular risk factors for osteoporosis by increasing bone perfusion. This is useful in two ways. First, it overcomes bone modeling limitations by reducing perfusion by increasing blood supply. Second, drug intervention for osteoporosis can be more effectively communicated to the bone by improving bone perfusion.

  Studies conducted under the supervision of the inventor have shown that 1) blood flow in the tibia and femur is enhanced when the device is active, and 2) the indication of perfusion is bone when the device is active Has demonstrated that it is no longer hypoxic.

  FIG. 6 shows oxyhemoglobin levels measured by infrared spectroscopy of the tibia during the stimulation cycle (on for 100 seconds and off for 100 seconds). Total blood volume (upper line) decreases during stimulation, indicating that the calf pump is promoting drainage, and increased oxyhemoglobin levels during stimulation indicate better oxygenation (hypoxic conditions) Reduction).

  FIG. 7 shows the results for the total of 12 subjects, showing the deoxyhemoglobin mean and standard deviation reduction relative to baseline. The device on the chart (labeled NMS) shows a significant decrease upon activation. As a scale idea, this is compared to the reduction obtained by increasing the blood supply using the tilt table method. This is a known hydrostatic step change, where the subject lies in a supine position on the tilting table and is fixed to the table, while the subject is tilted to stand upright to provide very large hydrostatic vascular stimulation. This chart is believed to be similar to the DVT parameter comparison on the device for foot flexion.

Previous examples have shown that devices and methods can be used to target new clinical goals. These include the following:
・ Lower limb arterial disease-peripheral arterial disease ・ Enhancement of lower limb lymphatic drainage ・ Heart disease ・ Fracture ・ Bone marrow perfusion enhancement-management of sickle cell crisis, ischemic bone marrow, stem cells, bone marrow collection methods-and drugs for bone marrow Improvement of cancer treatment by transporting limbs-Soft tissue damage of the lower limbs-skin and muscle bruises and minor lacerations-Sports training and rehabilitation-Restless legs syndrome (Witmark Ekbon syndrome)
-Enhancement of endothelium-derived nitric oxide and prostacyclin release.

[Example 5]
Discomfort Neuromuscular stimulation is commonly used to elicit muscle activity for various applications. These include exercise, rehabilitation, functional recovery (eg, drop foot stimulator), and recently, enhanced blood supply using a soleus muscle pump for various purposes.

  NMS has long been commonly used for functional recovery in insensitive persons (eg spinal cord injury). In such users, discomfort or pain associated with stimulation is not a problem.

  However, for users with sensations, discomfort or pain during stimulation is a problem and may be a factor limiting the applied stimulus level.

  In NMS, electrical stimulation is used to cause contraction of the skeletal muscle system. Unfortunately, efferent (motor) and afferent (sensory) nerves are bundled together in the same nerve conduit, with additional sensory nerves present in the skin. This means that in addition to stimulating motor nerves, NMS provides some stimulus to sensory nerves. When sensory signals reach the brain in large numbers and rapidly, it can be perceived as pain for some people.

  The relationship between electrode size and stimulus response has been known. It has also been found that the quality and tolerability of the stimulus is sensitive to the position of the electrode. These relationships were further investigated in a series of experiments by the inventors.

  One hypothesis tested is that the small electrodes can be more tolerated because they can accurately target the outer popliteal area of the radius without unnecessary irritation to the area surrounding the skin receptor It is a thing. This proved unreliable in this experiment. This finding can be explained as follows.

  While current density is usually greatest at the skin / electrode interface, the quality of muscle contraction is determined by the current density at the excitatory point.

  For a given current, a small electrode gives an increase in current density in the skin. However, this does not necessarily mean the maximum current density at the excitement point. The electrodes are necessarily separated from each other to prevent short circuits. Charge flows through the tissue from one electrode to the other in multiple indirect paths. Thus, the charge has the effect of taking a wider path in the tissue than the interface between the electrode and the skin, with the charge density being highest in the skin and lower in the tissue and at the nerve excitement points.

  Experiments were conducted in a variety of electrode arrangements to reduce the difference in current density between the skin interface and the desired stimulation point.

  It has proven advantageous to have two electrodes of different sizes. Neural excitement is achieved by depolarization of the nerve (usually having a positive extracellular charge and a negative intracellular charge), so the negative electrode (cathode) makes the nerve an action potential. A small cathode is placed in the exact area to be stimulated, and a larger anode is placed at a slightly separated site, resulting in a high current density only at the stimulation site, generally a low current density (below the action potential). It turns out to be advantageous.

  An improvement to this method is to provide an anode on both sides of the cathode, giving a greater spread of (low) current density at the anode. Two possible electrode embodiments include the three parallel strip types of FIG. 8 (negative in the middle) and the target type of FIG. 9 (negative bullseye). The target variant has a closer or open outer circle, ellipse.

  The electrode structure was experimentally tested.

  Ten healthy subjects ranging from 24 to 50 years old were used. Ask each subject to mark a standard 10 cm line segment where their senses are located on the scale from no discomfort (leftmost) to extreme pain (rightmost) The visual analog score was measured. The system was chosen to normalize their scores relative to the existing electrode configurations and corrugated standard sensations used in previous studies.

  A normalized discomfort score was derived for each configuration based on the horizontal distance between the configuration VAS and the standard configuration VAS. Thus, a positive score indicates more unpleasant and a negative score indicates more comfortable.

  A to F in FIG. 10 show the electrode configuration used.

  Two waveforms were used, symmetric and asymmetric (see FIG. 11). In both cases, the overall charge is balanced (area A is equal) and galvanic stimulation is not considered.

  Table 2 gives the keys of the electrode / waveform combinations used.

  FIG. 12 shows each configuration as a number on the x axis. For each one, the median normalized VAS is shown with a blue bar, and the range between the first and third quartiles is shown with whiskers.

  It can be seen that for all asymmetric waveforms, the most preferred combination is C, D, then B.

  Note that configuration 1 is zero in all cases by definition.

  FIG. 13 shows the normalized VAS assessment for each subject with lines by color. This makes it clearer that an asymmetric waveform is preferred.

  The optimal configuration is a symmetric / targeted arrangement, where the negative electrode is in the middle and the positive electrode is larger than the negative electrode. As for the waveform, it shows that an asymmetrical but well-balanced charge (small but long-term negative current following a large positive spike) is optimal for comfort.

  A preferred embodiment of the device according to the invention is shown in FIGS. The device 10 includes a flexible, non-stretchable thermoplastic elastomer substrate 12 that includes an elongated tongue 14 at one end and a molded recess 16 at the other end.

  A positive electrode 18 and a negative electrode 20 are printed on the tongue portion 14. The positive electrode is slightly larger than the negative electrode. Each electrode includes a conductive track 22, 24 that leads from the electrode to a respective contact point 26, 28 located in the recess 16.

  Although not shown, an insulating strip is placed between the positive track 22 and the negative electrode 20 and a similar strip is placed at the edge of the tongue to prevent unwanted current leakage.

  Disposed within the recess 16 is a battery (not shown) and a PCB (not shown) including appropriate circuitry for controlling the electrodes. Together with the conductive tracks 22, 24 and contact points 26, 28, the PCB forms a complete circuit. A plastic cover is ultrasonically welded onto the recess 16 to seal the part. A gel layer is placed over the entire device 10 to provide electrical contact with the user's limb and to help keep the device adhered to the user. The gel can be protected during transport by a re-stickable backing layer.

  The outer surface of the recess 16 is formed with an integrated diaphragm button 30 and an opening 32 for displaying an LED. The buttons 30 are arranged to contact the corresponding buttons 30 on the battery housing or PCB to activate the device. Opening 32 displays an LED indicating whether the device is operating.

10 device 12 substrate 14 tongue portion 16 recessed portion 18 positive electrode 20 negative electrode 22, 24 conductive track 26, 28 contact point 30 button 32 opening

Claims (3)

A positive electrode and a negative electrode for applying electrical stimulation to nerves distributed in opposing leg muscles of a patient to cause isometric contraction of the leg muscles; and a power supply connectable to the positive electrodes and the negative electrodes; A control means for actuating the positive electrode and the negative electrode, comprising:
The device comprises an elongated flexible substrate;
The elongated flexible substrate includes an elongated tongue at one end and a molding recess at the other end,
The electrode is mounted on or directly printed on the elongated tongue with the positive electrode spaced longitudinally from the negative electrode along the substrate;
The positive electrode is larger than the negative electrode;
The power source and the control means are arranged in a molded recess,
The power source is connected to the electrode by a conductive track;
The conductive track of the positive electrode is separated from the negative electrode by one or more insulating strips or regions;
The insulating strip or region is arranged at the edge of the tongue to prevent undesired leakage of current;
The device further includes a push button to activate or deactivate the device;
device.   The device of claim 1, further comprising a conductive gel covering the electrode.   The device of claim 1 in combination with a defibrillator.

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